Abstract

Background: Diabetes is a significant risk factor for cardiovascular disease, but optimal glycemic control strategies remain unclear. In particular, trials of intensive glycemic control have highlighted a tension between increased mortality risk and macrovascular benefits. In this study we aimed to assess whether the burden of coronary artery disease (CAD) modifies the association between glycemic control and short-term mortality. Methods: We studied veterans with diabetes who underwent elective cardiac catheterization between 2005 and 2013 in a retrospective analysis of data from the VA Clinical Assessment, Reporting, and Tracking (CART) Program. Primary exposures were time-varying HbA1c over two years of follow-up after index catheterization, categorized as <6%, 6-6.49%, 6.5-6.99%, 7-7.99%, 8-8.99%, and >=9%, and burden of CAD, categorized as no CAD, non-obstructive CAD, or obstructive CAD. Primary outcome was two-year all-cause mortality. A total of 17394 participants had, on average, five HbA1c measurements over two years of follow-up. We used multivariable Cox proportional hazards regression to estimate the association between HbA1c and mortality, adjusting for demographic and clinical covariates and CAD burden, and including a term for interaction between HbA1c and CAD burden. Results: In adjusted models with 6.5 ≤ HbA1c ≤ 6.99% as the reference category, HbA1c < 6% was associated with increased risk of mortality (HR 1.55 [1.25, 1.92]), whereas HbA1c categories above 7% were not. We observed significant interaction between glycemic control and CAD burden (interaction p=0.0005); the increased risk of short-term mortality at HbA1c < 6% was limited to individuals with non-obstructive and obstructive CAD (Figure 1). Conclusions: HbA1c below 6% was associated with increased risk of short-term mortality, but only in individuals with CAD. CAD burden may thus inform individualized diabetes management strategies, specifically treatment de-escalation in individuals with any angiographically-defined CAD.

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